Quinazoline compounds and their use in perfume compositions

ABSTRACT

The present invention relates to novel quinazoline compounds and their use in perfume compositions. The novel quinazoline compounds of the present invention are represented by the following formula: 
     
       
         
         
             
             
         
       
         
         
           
             an isomer or a mixture of isomers thereof, 
             wherein the broken line represents a single or double bond.

FIELD OF THE INVENTION

The present invention relates to new chemical entities and theincorporation and use of the new chemical entities as fragrancematerials.

BACKGROUND OF THE INVENTION

There is an ongoing need in the fragrance industry to provide newchemicals to give perfumers and other persons the ability to create newfragrances for perfumes, colognes and personal care products. Those withskill in the art appreciate how differences in the chemical structure ofthe molecule can result in significant differences in the odor, notesand characteristics of a molecule. These variations and the ongoing needto discover and use the new chemicals in the development of newfragrances allow the perfumers to apply the new compounds in creatingnew fragrances.

SUMMARY OF THE INVENTION

The present invention provides novel compounds and their unexpectedadvantageous use in enhancing, improving or modifying the fragrance ofperfumes, colognes, toilet water, fabric care products, personalproducts and the like.

More specifically, the present invention relates to novel quinazolinecompounds represented by Formula I set forth below:

isomers or mixtures of isomers thereof,

wherein the broken line represents a single or double bond.

Another embodiment of the present invention relates to a fragrancecomposition comprising the novel compounds provided above.

Another embodiment of the present invention relates to a fragranceproduct comprising the compounds provided above.

Another embodiment of the present invention relates to a method ofimproving, enhancing or modifying a fragrance formulation through theaddition of an olfactory acceptable amount of the novel compoundsprovided above.

These and other embodiments of the present invention will be apparent byreading the following specification.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the present invention may be represented by thefollowing structures:

wherein * indicates a chiral center.

The isomeric forms of Formula II and Formula III may be furtherrepresented, respectively, by the following structures:

Those with the skill in the art will appreciate that

-   Formula II is    6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline;-   Formula III is    6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline;-   Formula IV is    8S-6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline;-   Formula V is    8R-6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline;-   Formula VI is    cis-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline;    and-   Formula VII is    trans-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline.

The compounds of the present invention can be prepared from Cashmeran™(commercially available at International Flavors & Fragrances Inc.) orits hydrogenated form according to the reaction scheme below, thedetails of which are specified in the Examples. Materials were purchasedfrom Aldrich Chemical Company unless noted otherwise.

Additionally, a cis-hexahydro-quinazoline is obtained. Atetrahydro-quinazoline from the above scheme is further treated withisopropanol (referred to as “IPA” hereinafter) and palladium on carbon(referred to as “Pd/C” hereinafter) in the presence of hydrogen toprovide 90% cis- and 10% trans-hexahydro-quinazolines.

Those with skill in the art will recognize that the isomeric productsobtained as described above can be further separated using techniquesknown to those with skill in the art. Suitable techniques include, forexample, distillation and chromatography such as high performance liquidchromatography, referred to as HPLC, particularly silica gelchromatograph, and gas chromatography trapping known as GC trapping.Yet, commercial products are mostly offered as isomeric mixtures.

The use of the compounds of the present invention is widely applicablein current perfumery products, including the preparation of perfumes andcolognes, the perfuming of personal care products such as soaps, showergels, and hair care products, fabric care products, air fresheners, andcosmetic preparations. The present invention can also be used to perfumecleaning agents, such as, but not limited to detergents, dishwashingmaterials, scrubbing compositions, window cleaners and the like.

In these preparations, the compounds of the present invention can beused alone or in combination with other perfuming compositions,solvents, adjuvants and the like. The nature and variety of the otheringredients that can also be employed are known to those with skill inthe art. Many types of fragrances can be employed in the presentinvention, the only limitation being the compatibility with the othercomponents being employed. Suitable fragrances include but are notlimited to fruits such as almond, apple, cherry, grape, pear, pineapple,orange, strawberry, raspberry; musk, flower scents such aslavender-like, rose-like, iris-like, carnation-like. Other pleasantscents include herbal and woodland scents derived from pine, spruce andother forest smells. Fragrances may also be derived from various oils,such as essential oils, or from plant materials such as peppermint,spearmint and the like.

A list of suitable fragrances is provided in U.S. Pat. No. 4,534,891,the contents of which are incorporated by reference as if set forth inits entirety. Another source of suitable fragrances is found inPerfumes, Cosmetics and Soaps, Second Edition, edited by W. A. Poucher,1959. Among the fragrances provided in this treatise are acacia, cassie,chypre, cyclamen, fern, gardenia, hawthorn, heliotrope, honeysuckle,hyacinth, jasmine, lilac, lily, magnolia, mimosa, narcissus, freshly-cuthay, orange blossom, orchid, reseda, sweet pea, trefle, tuberose,vanilla, violet, wallflower, and the like.

The term “improving” in the phrase “improving, enhancing or modifying afragrance formulation” is understood to mean raising the fragranceformulation to a more desirable character. The term “enhancing” isunderstood to mean making the fragrance formulation greater ineffectiveness or providing the fragrance formulation with an improvedcharacter. The term “modifying” is understood to mean providing thefragrance formulation with a change in character.

The terms “fragrance formulation”, “fragrance composition”, and “perfumecomposition” are understood to mean the same and refer to a formulationthat is intended for providing a fragrance character to a perfume, acologne, toilet water, a personal product, a fabric care product, andthe like. The fragrance formulation of the present invention is acomposition comprising a compound of the present invention.

Olfactory effective amount is understood to mean the amount of compoundin perfume compositions the individual component will contribute to itsparticular olfactory characteristics, but the olfactory effect of theperfume composition will be the sum of the effects of each of theperfumes or fragrance ingredients. Thus the compounds of the inventioncan be used to alter the aroma characteristics of the perfumecomposition, or by modifying the olfactory reaction contributed byanother ingredient in the composition. The amount will vary depending onmany factors including other ingredients, their relative amounts and theeffect that is desired.

The amount of the compounds of the present invention employed in afragrance formulation varies from about 0.005 to about 70 weightpercent, preferably from 0.005 to about 50 weight percent, morepreferably from about 0.5 to about 25 weight percent, and even morepreferably from about 1 to about 10 weight percent. Those with skill inthe art will be able to employ the desired amount to provide desiredfragrance effect and intensity. In addition to the compounds of thepresent invention, other materials can also be used in conjunction withthe fragrance formulation. Well known materials such as surfactants,emulsifiers, polymers to encapsulate the fragrance can also be employedwithout departing from the scope of the present invention.

When used in a fragrance formulation this ingredient provides sweet,floral, ambery, musky, woody, and powdery notes to make the fragranceformulation more desirable and noticeable, and add the perception ofvalue. The odor qualities found in this material assist in beautifyingand enhancing the finished accord as well as improving the performanceof the other materials in the fragrance.

The following are provided as specific embodiments of the presentinvention. Other modifications of this invention will be readilyapparent to those skilled in the art. Such modifications are understoodto be within the scope of this invention. As used herein all percentagesare weight percent unless otherwise noted, ppm is understood to standfor parts per million, L is understood to be liter, mL is understood tobe milliliter, g is understood to be gram, mol is understood to be mole,and mmHg be millimeters (mm) of mercury (Hg). IFF as used in theexamples is understood to mean International Flavors & Fragrances Inc.,New York, N.Y., USA.

Example I

Preparation of6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula II)

A 5 L reaction vessel was charged with Cashmeran™ (412 g, 2.0 mol,commercially available at IFF), formamidine acetate (1030 g, 10.0 mol),and butanol (1.2 L). The reaction mixture was heated to 118° C. for 4hours and then cooled to 25° C. The reaction mixture was washed twicewith brine (1 L) and purified by vacuum distillation to afford6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(260 g) having a boiling point of 140° C. at a pressure of 1.6 mmHgFurther recrystallization from ethanol afforded a solid with a meltingpoint of 80.0° C.

¹H NMR (CDCl₃, 500 MHz): 8.90 ppm (s, 1H), 8.31 ppm (s, 1H), 2.77-2.82ppm (m, 2H), 2.35-2.41 ppm (m, 1H), 2.25-2.32 ppm (m, 1H), 1.74 ppm (q,1H, J=7.37 Hz), 1.38 ppm (s, 3H), 1.23 ppm (s, 3H), 1.11 ppm (s, 3H),0.95 ppm (d, 3H, J=7.40 Hz), 0.93 ppm (s, 3H).

The compound was described as having musky, ambery, and powdery notes.

Example II

Preparation of6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula III)

Dihydrocashmeran was obtained via the hydrogenation of Cashmeran™. A 3 Lreaction vessel was charged with dihydrocashmeran (255 g, 1.2 mol),formamidine acetate (642 g, 6.2 mol), and butanol (1.2 L). The reactionmixture was heated to 118° C. for 4 hours and then cooled to 25° C. Thereaction mixture was washed twice with brine (1 L) and purified byvacuum distillation to afford a 40:60 cis/trans mixture of6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(200 g) having a boiling point of 153° C. at a pressure of 2.0 mmHg Thecis/trans structures were confirmed by NMR analysis by GC trapping.

Trans-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline

¹H NMR (CDCl₃, 500 MHz): 8.92 ppm (s, 1H), 8.37 ppm (s, 1H), 2.75-2.93ppm (m, 2H), 2.65 ppm (d, J=12.6 Hz, 1H), 1.20-2.10 ppm (m, 4H), 1.32ppm (s, 3H), 0.99 ppm (s, 3H), 0.95 ppm (s, 3H), 0.84 ppm (d, J=7.5 Hz,3H), 0.71 ppm (s, 3H).

Cis-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline

¹H NMR (CDCl₃, 500 MHz): 8.96 ppm (s, 1H), 8.39 ppm (s, 1H), 3.00 ppm(d, J=9.7 Hz, 1H), 2.52-2.79 ppm (m, 2H), 1.25-2.15 ppm (m, 4H), 1.42ppm (s, 3H), 1.10 ppm (s, 3H), 0.92 ppm (s, 3H), 0.84 ppm (d, J=7.3 Hz,3H), 0.54 ppm (s, 3H).

The compounds were described as having ambery, musky, and woody notes.

Example III

Preparation ofcis-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula VI)

A 500 mL zipper autoclave was charged with6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(100 g, synthesized as above in EXAMPLE I), IPA (100 mL), and Pd/C (1g). The autoclave was sealed, purged with nitrogen, and then pressurizedwith hydrogen. The reaction mixture was heated to 180° C. for 4 hoursand subsequently cooled to 25° C. The autoclave was vented and purgedwith nitrogen. The catalyst was removed by filtration through celite. Acrude mass containing the major productcis-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(90%) was obtained. The crude mass was evaluated by gas chromatographyolfactometry.Cis-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazolinewas described as having a musky character. In addition, the minorproduct in the crude mass,trans-6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula VII) (10%), was also evaluated and described as having anambery character.

Example IV

The fragrance formulas exemplified as follows demonstrated that theaddition of6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula III) containing a 40:60 cis/trans isomeric mixture provided amusky character to the fragrance formula.

Ingredient Parts (g) Parts (g) Kharismal ™ 175 175 Ethylene Brassylate50 50 Dipropylene Glycol 34 34 Iso Gamma Super ™ 30 30 HydroxyCitronellal Pure 15 15 Indasan 10 10 Amberiff 20% IPM 10 10L-Citronellol 8 8 Beta Ionone Extra 5 5 Linalyl Acetate 5 5 Ambrettolide3 3 Geraniol 980 3 3 Healingwood ™ 1 1 Amber Xtreme ™ 1% DPG 1 1 FormulaIII 10 — DPG — 10 Total 360 360

The above fragrance formulas had floral and woody characters. Theaddition of6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula III) intensified the floral and woody notes and provided amusky undertone.

Example V Fragrance formulation containing6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula II)

Ingredient Parts (g) Santaliff ™ 24 Phenoxanol ™ 32 Coumarin 28 CyclamalExtra 1 Eth Vanillin 7 Geraniol 980 Pure 1 Hedione ™ 60 Amy CinnamicAldehyde 60 Heliotropine 17 Hexyl Cinnamic Ald 16 Beta Ionone Extra 6Iso E Super ™ 70 Lyral ™ 16 lillial ™ 160 Lilianth 20 Methyl IononeGamma A 73 Veramoss 2 Peru Balsam Oil India 3 Prenyl Acetate 1 MethylCedryl Ketone 40 Methyl Phenyl Acetate 1 Aubepine 4 Benzoin 10 CedrolTex 3

Example V Continued

Ingredient Parts (g) Citronellol Extra 3 Geraniol Coeur 4 MethylCinnamate 3 Styrax Alva Ess 2 Vanillin ex Lignin 12 Cananga Java Native5 Formula II 20 Total 704

6,7,8,9-Tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline(Formula II) imparted diffusive floral and soft powdery characters to afragrance formula.

What is claimed is:
 1. A compound6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline. 2.A fragrance formulation containing an olfactory acceptable amount of6,7,8,9-tetrahydro-7,7,8,9,9-pentamethyl-5H-cyclopenta[H]quinazoline. 3.The fragrance formulation of claim 2 further comprising a productselected from the group consisting of a perfume, a cologne, toiletwater, a cosmetic product, a personal care product, a fabric careproduct, a cleaning product, and an air freshener.
 4. The fragranceformulation of claim 3, wherein the cleaning product is selected fromthe group consisting of a detergent, a dishwashing composition, ascrubbing compound, and a window cleaner.
 5. The fragrance formulationof claim 2, wherein the olfactory acceptable amount is from about 0.005to about 50 weight percent of the fragrance formulation.
 6. Thefragrance formulation of claim 2, wherein the olfactory acceptableamount is from about 0.5 to about 25 weight percent of the fragranceformulation.
 7. The fragrance formulation of claim 2, wherein theolfactory acceptable amount is from about 1 to about 10 weight percentof the fragrance formulation.